Furosemide

Furosemide is a loop diuretic with a chlorinated sulfonamide group that can be administered p.o. and i.v.. Furosemide is considered the lead substance of the loop diuretics. Loop diuretics are inhibitors of the Na+/K+/2Cl- - symporter in the thick ascending limb of the loop of Henle of the nephron. Furosemide is a potent agent in acute therapy of any type of edema due to its rapid and potent action (Fallahzadeh MA et al. 2017). It is important to note that already in intravenous monotherapy, but especially in the combination of loop diuretics with other diuretics, there is a risk of hypokalemia with life-threatening arrhythmias. In this respect, strict monitoring of electrolytes is necessary.

Heart failure NYHA I-IV when water retention is clinically present (Owen DR et al. 2015).

See below: Heart failure: Drug therapy in clinical use.

Acute renal failure: In overhydration, furosemide 20-100 mg/hour i.v., can be increased to max. 1,500 mg/day in the short term under intensive medical observation

Oedema of other cause

Furosemide 20 mg p.o 1-1-0; increase dose up to 250 mg i.v./p.o. 1-1-0 considering renal function!

Dose adjustments:

• Renal insufficiency
• Furosemide 250 mg/day should only be used from a GFR <20 mL/min.
• Note necessary dose increase on the one hand and worsening of renal function at too high doses on the other hand.
• Liver insufficiency

Use in children

• Furosemide 2 mg/kg bw preferably p.o. up to a maximum of 40 mg/day

Hyponatremia (clinic: apathy, calf cramps, loss of appetite, weakness, drowsiness, vomiting, and confusional states).

Hypokalemia (clinic: muscle weakness, paresthesias, paresis; vomiting, constipation, meteorism; polyuria, polydipsia, and arrhythmias).

Dermatologic UAW:

• Among dermatologic UAWs, phototoxic reactions are especially noteworthy. The explanation for this lies in the chlorine substitution of the chemical structure of furosemide. The photochemical activity is due to a UV-induced dissociation of the chlorine substituent, which leads to radical reactions with lipids, proteins and DNA. Non-UV-provoked lichenoid exanthema has also been observed (Arias-Santiago S et al. 2010) . Bermecia: see also under hydrochlorothiazide.
• Furthermore, urticaria as well as anaphylactic reactions have been described (Domínguez-Ortega J et al. 2003).
• Occasionally, "pseudoporphyria-like clinical pictures (Petersen CS et al. 1992) and the occurrence of bullous pemphigoid have been described (Lee JJ et al. 2006).
• In rare cases, furosemide can cause uncharacteristic "eczematous manifestations"; furthermore, purpura and erythema multiforme (also bullous variants).
• Isolated reports refer to Stevens-Johnson syndrome (Wright AA et al. 2010), DRESS syndrome (James J et al. 2018) and Sweet syndrome (Govindarajan G et al. 2005).

The effect of furosemide may be affected by concomitant treatment with the following drugs or groups of drugs.

Glucocorticoids, carbenoxolone or laxatives may lead to increased potassium losses with the risk of developing a potassium deficiency state.

Non-steroidal anti-inflammatory drugs, e.g. indomethacin and acetylsalicylic acid may weaken the effect of furosemide-.

If circulating blood volume decreases during treatment with furosemide, concomitant administration of non-steroidal anti-inflammatory drugs may precipitate acute renal failure.

Furosemide may increase the adverse effects of nephrotoxic drugs (e.g., antibiotics such as aminoglycosides, cephalosporins, polymyxins).

Therapy with cisplatin may increase the nephrotoxicity of cisplatin.

An attenuation of the effect of furosemide has been described with concomitant administration of phenytoin.

Sucralfate decreases the absorption of furosemide from the intestine.

Concomitant treatment with certain cardiac agents (glycosides) may increase myocardial sensitivity to these cardiac agents if potassium or magnesium deficiency develops during treatment with furosemide. There is an increased risk of cardiac arrhythmias (ventricular arrhythmias including torsade de pointes) with concomitant use of drugs that may cause "prolonged QT interval syndrome" (e.g., terfenadine) and in the presence of electrolyte disturbances. The side effects of high-dose salicylates may be increased with concomitant use of furosemide.

Ototoxicity: The ototoxicity of aminoglycosides (e.g. kanamycin, gentamicin, tobramycin) and other hearing-damaging drugs may be increased with concomitant administration of furosemide. Any hearing impairment that occurs may be irreversible.

Lithium: Concomitant administration of furosemide and lithium may result in an enhancement of the cardiac and neurotoxic effects of lithium. Therefore, it is recommended that blood lithium levels be carefully monitored in patients receiving this combination.

When other antihypertensive drugs are used concomitantly with furosemide, a greater drop in blood pressure is to be expected. Massive drops in blood pressure, including shock, and worsening of renal function (acute renal failure in isolated cases) have been observed, particularly when an ACE inhibitor or angiotensin II receptor antagonist is given for the first time or for the first time at a higher dose.

The effect of theophylline or curare-type drugs (muscle relaxants) may be enhanced by furosemide.

Other Interactions:

Gout: Concomitant use of ciclosporin A and furosemide is associated with an increased risk of arthritis urica, as a result of an increase in blood uric acid levels caused by furosemide and impairment of renal excretion of uric acid by ciclosporin.

Taking furosemide with food: large amounts of licorice in combination with furosemide may cause increased potassium losses.

Traffic ability and ability to operate machinery: Even when used as directed, furosemide may alter the ability to react to such an extent that the ability to actively participate in road traffic, to operate machinery or to work without a safe footing is impaired. This applies to a greater extent when starting treatment, increasing the dose and changing the preparation as well as in combination with alcohol.

moderate to severe hepatic insufficiency

Gravidity/Lactation

Gravidity: Furosemide is not recommended during pregnancy.

Lactation

oligo-anuric patients

1. Domínguez-Ortega J et al (2003) Anaphylaxis to oral furosemide. Allergol Immunopathol (Madr) 31:345-347.
2. Fallahzadeh MA et al. (2017) Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus.
3. Furosemide and Hydrochlorothiazide Followed by Furosemide for the Treatment of
4. Adults With Nephrotic Edema: A Randomized Trial. Am J Kidney Dis 69:420-427.
5. Govindarajan G et al (2005) Sweet syndrome associated with furosemide. South Med J 98:570-572.
6. James J et al (2018) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Secondary to Furosemide: Case Report and Review of Literature. Am J Case Rep 19:163-170.
7. Lee JJ et al (2006) Furosemide-induced bullous pemphigoid: case report and review of literature. J Drugs Dermatol 5:562-564.
8. Owen DR et al (2015) Intravenous furosemide for Acute Decompensated Congestive Heart Failure: What Is the Evidence? Clin Pharmacol Ther 98:119-121.
9. Petersen CS et al (1992) Pseudoporfyri [pseudoporphyria]. Ugeskr Laeger 154:1713-1715.
10. Thestrup-Pedersen K (1987) Adverse reactions in the skin from anti-hypertensive drugs. Dan Med Bull 34 Suppl 1:3-5.
11. Wright AA et al (2010) Stevens-Johnson syndrome associated with furosemide: a case report. J Pharm Pract 23:367-370.